Exosomes released from breast cancer carcinomas stimulate cell movement

For metastasis to occur cells must communicate with to their local environment to initiate growth and invasion. Exosomes have emerged as an important mediator of cell-to-cell signalling through the transfer of molecules such as mRNAs, microRNAs, and proteins between cells. Exosomes have been proposed to act as regulators of cancer progression. Here, we study the effect of exosomes on cell migration, an important step in metastasis. We performed cell migration assays, endocytosis assays, and exosome proteomic profiling on exosomes released from three breast cancer cell lines that model progressive stages of metastasis. Results from these experiments suggest: (1) exosomes promote cell migration and (2) the signal is stronger from exosomes isolated from cells with higher metastatic potentials; (3) exosomes are endocytosed at the same rate regardless of the cell type; (4) exosomes released from cells show differential enrichment of proteins with unique protein signatures of both identity and abundance. We conclude that breast cancer cells of increasing metastatic potential secrete exosomes with distinct protein signatures that proportionally increase cell movement and suggest that released exosomes could play an active role in metastasis

Improving dialysis adherence for high risk patients using automated messaging: Proof of concept

AbstractComorbidities and socioeconomic barriers often limit patient adherence and self-management with hemodialysis. Missed sessions, often associated with communication barriers, can result in emergency dialysis and avoidable hospitalizations. This proof of concept study explored using a novel digital-messaging platform, EpxDialysis, to improve patient-to-dialysis center communication via widely available text messaging and telephone technology. A randomized controlled trial was conducted through Washington University-affiliated hemodialysis centers involving ESRD patients with poor attendance, defined as missing 2–6 sessions over the preceding 12 weeks. A cross-over study design evaluated appointment adherence between intervention and control groups. Comparing nonadherence rates eight weeks prior to enrollment, median appointment adherence after using the system increased by 75%, and median number of unintended hospitalization days fell by 31%. A conservative cost-benefit analysis of EpxDialysis demonstrates a 1:36 savings ratio from appointment adherence. EpxDialysis is a low-risk, cost-effective, intervention for increasing hemodialysis adherence in high-risk patients, especially at centers caring for vulnerable and low-income patients.</jats:p

Provincial screening rates for chronic diseases of lifestyle, cancers and HIV in a health-insured population

Background. Screening for asymptomatic diseases can reduce the burden of morbidity and mortality in all population groups. There is widespread geographical variation in the quality of care. Few data are available on national screening rates in South Africa and how these vary across the provinces.Objective. To examine screening rates for chronic diseases of lifestyle (CDL), HIV and cancer in a privately insured population for a singleinsurer across all nine provinces in South Africa, and to determine whether or not there are any differences between the provinces.Method. Screening rates were calculated as the proportion of eligible members who had received screening tests during 2011 in eachprovince. Mean screening rates were compared between Gauteng and the other eight provinces.Results. Nationwide screening rates were 20.5% for CDL, 8.2% for HIV and 31.9% for cancer. Despite similar insurance coverage, screening ratesranged from 0.3% to 0.95% lower in other provinces compared with Gauteng. Of all the provinces, Gauteng had the highest annual screeningrates for CDL, breast cancer, prostate cancer and HIV (p&lt;0.001), while the Western Cape had the highest rate for cervical cancer (p&lt;0.001).Conclusion. There is much variation in preventive care utilisation across the provinces within this health-insured population. Provinces with more abundant healthcare resources have higher screening rates. Further research is required to understand the reasons for the variation, given equal payment access

Radiographic viewing conditions at Johannesburg Hospital

Purpose: To measure the luminance level of X-ray viewing boxes and ambient lighting levels in reporting rooms as a quality assurance procedure, and to compare the results with those recommended by the Directorate of Radiatio

The effects of obesity, smoking, and excessive alcohol intake on healthcare expenditure in a comprehensive medical scheme

Background. Health risks such as tobacco use, excessive alcohol consumption and unhealthy body weight contribute to the development of chronic health problems.Objective. To estimate the associations of tobacco use, excessive alcohol consumption and obesity with healthcare expenditure and chronic diseases among South Africans on a comprehensive medical scheme. Methods. We performed a cross-sectional analysis of health survey and medical claims data for 70 000 South Africans during 2010. Results. Moderately obese individuals, with a body mass index (BMI) of 30 - 35 kg/m2 averaged R2 300 (11%) higher annual medical expenditure in the year 2010 than never-smokers with a BMI &lt;30 kg/m2. This increase is comparable with being a current or past smoker (expenditure increase by R2 600; 13%). Severely obese individuals (BMI &gt;35 kg/m2), however, had increased healthcare costs of R4 400 (23% increase). This exceeds the difference between a 40- and a 50-year-old (increase of R3 200). Being overweight or excessive consumption of alcohol was not significantly associated with medical expenditures. Absolute and relative excess expenditures associated with these health risks are higher among older individuals. In the 54 - 69-year age group, estimated additional expenses were R6 200 for smoking (20% increase over never-smokers with BMI &lt;30 kg/m2), R6 600 for moderate obesity (21%) and R15 800 for severe obesity (51% increase). Overweight or heavy drinking was not statistically significantly associated with healthcare expenditure.Conclusion. Obesity and tobacco use are associated with significantly increased healthcare expenditure. Severe obesity doubles these excess costs.

Autophagy in Idiopathic Pulmonary Fibrosis

Background: Autophagy is a basic cellular homeostatic process important to cell fate decisions under conditions of stress. Dysregulation of autophagy impacts numerous human diseases including cancer and chronic obstructive lung disease. This study investigates the role of autophagy in idiopathic pulmonary fibrosis. Methods: Human lung tissues from patients with IPF were analyzed for autophagy markers and modulating proteins using western blotting, confocal microscopy and transmission electron microscopy. To study the effects of TGF-β1 on autophagy, human lung fibroblasts were monitored by fluorescence microscopy and western blotting. In vivo experiments were done using the bleomycin-induced fibrosis mouse model. Results: Lung tissues from IPF patients demonstrate evidence of decreased autophagic activity as assessed by LC3, p62 protein expression and immunofluorescence, and numbers of autophagosomes. TGF-β1 inhibits autophagy in fibroblasts in vitro at least in part via activation of mTORC1; expression of TIGAR is also increased in response to TGF-β1. In the bleomycin model of pulmonary fibrosis, rapamycin treatment is antifibrotic, and rapamycin also decreases expression of á-smooth muscle actin and fibronectin by fibroblasts in vitro. Inhibition of key regulators of autophagy, LC3 and beclin-1, leads to the opposite effect on fibroblast expression of á-smooth muscle actin and fibronectin. Conclusion: Autophagy is not induced in pulmonary fibrosis despite activation of pathways known to promote autophagy. Impairment of autophagy by TGF-β1 may represent a mechanism for the promotion of fibrogenesis in IPF

Chiral emergence in multistep hierarchical assembly of achiral conjugated polymers

Intimately connected to the rule of life, chirality remains a long-time fascination in biology, chemistry, physics and materials science. Chiral structures, e.g., nucleic acid and cholesteric phase developed from chiral molecules are common in nature and synthetic soft materials. While it was recently discovered that achiral but bent core mesogens can also form chiral helices, the assembly of chiral microstructures from achiral polymers has rarely been explored. Here, we reveal chiral emergence from achiral conjugated polymers for the first time, in which hierarchical helical structures are developed through a multistep assembly pathway. Upon increasing concentration beyond a threshold volume fraction, pre-aggregated polymer nanofibers form lyotropic liquid crystalline (LC) mesophases with complex, chiral morphologies. Combining imaging, X-ray and spectroscopy techniques with molecular simulations, we demonstrate that this structural evolution arises from torsional polymer molecules which induce multiscale helical assembly, progressing from nano- to micron scale helical structures as the solution concentration increases. This study unveils a previously unknown complex state of matter for conjugated polymers that can pave way to a new field of chiral (opto)electronics. We anticipate that hierarchical chiral helical structures can profoundly impact how conjugated polymers interact with light, transport charges, and transduce signals from biomolecular interactions and even give rise to properties unimagined before.Comment: 47 pages, 7 figure

Deciphering the Finger Prints of Brain Cancer Glioblastoma Multiforme from Four Different Patients by Using Near Infrared Raman Spectroscopy

To explore the effectiveness of Raman spectra to diagnose brain cancer glioblastoma multiforme (GBM), we investigated the Raman spectra of single cell from four different GBM cell lines developed from four different patients and analyzed the spectra. The Raman spectra of brain cancer (GBM) cells were similar in all these cell lines. The results indicate that Raman spectra can offer the experimental basis for the cancer diagnosis and treatment

Greater Motor Evoked Torque in ACLR Patients during Force Reproduction Task Compared to Health Controls

Persistent quadriceps dysfunction following anterior cruciate ligament reconstruction (ACLR) may lead to further pathological complication. Quadriceps weakness has been linked to corticospinal excitability. However, it remains unclear how this altered corticospinal excitability contributes to ACLR patients during knee strength tasks when compared to healthy controls. PURPOSE: The purpose of this study was to examine force reproduction strategies during isometric knee extension between ACLR patients and healthy controls. METHODS: Five ACLR (20.40±1.67yrs, 72.12±12.87kg, 171.07±7.40cm) participants and five matched healthy controls (21.00±1.73yrs, 65.77±13.61kg, 166.62±11.99cm) performed an isometric force reproduction task. They were instructed to maintain 10% of maximal voluntary isometric contraction (MVIC) in response to unexpected Transcranial Magnetic Stimulation (TMS) over the primary motor cortex, targeting the quadriceps. The TMS stimulations were randomly delivered at two different intensities: 120% and 140% active motor threshold (AMT). Additionally, resting twitch torque (RTT) was measured by delivering TMS stimulations at 100% intensity over the quadriceps. Motor evoked torque (MET, %) was calculated by normalizing the 120% and 140% peak change relative to 10% MVIC by RTT values. Comparisons were made using 2-way ANOVAs with one within factor (intensity, 2 levels) and one between factor (group, 2 levels). RESULTS: A significant TMS intensity by group interaction was observed for MET (F[1,8] = 18.639, p = 0.003). The ACLR group had higher MET than the control group at AMT 140% (196.12±40.83 vs 106.69±34.01%, p = 0.006), while there was no difference at 120% (117.19±36.72 vs 69.06±44.18%, p = 0.098). CONCLUSION: The ACLR group produced similar torque changes to the CONT group at 120% of AMT, but more torque changes at the higher intensity. This may indicate protective neural adaptations responsible for force production, particularly at the corticospinal tract. However, this altered corticospinal excitability may also cause heightened quadriceps contraction during high-intensity tasks, potentially resulting in anterior ACL translation, which could put stress on the ACL and increase the risk of re-tear

Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice

HIV-1 infections are generally initiated at mucosal sites. Thus, IgA antibody, which plays pivotal roles in mucosal immunity, might efficiently prevent HIV infection. However, mounting a highly effective HIV-specific mucosal IgA response by conventional immunization has been challenging and the potency of HIV-specific IgA against infection needs to be addressed in vivo. Here we show that the polymeric IgA form of anti-HIV antibody inhibits HIV mucosal transmission more effectively than the monomeric IgA or IgG1 form in a comparable range of concentrations in humanized mice. To deliver anti-HIV IgA in a continual manner, we devised a hematopoietic stem/progenitor cell (HSPC)–based genetic approach using an IgA gene. We transplanted human HSPCs transduced with a lentiviral construct encoding a class-switched anti-HIV IgA (b12-IgA) into the humanized bone marrow-liver-thymus (BLT) mice. The transgene was expressed specifically in B cells and plasma cells in lymphoid organs and mucosal sites. After vaginal HIV-1 challenge, mucosal CD4^+ T cells in the b12-IgA–producing mice were protected from virus-mediated depletion. Similar results were also obtained in a second humanized model, “human immune system mice.” Our study demonstrates the potential of anti-HIV IgA in immunoprophylaxis in vivo, emphasizing the importance of the mucosal IgA response in defense against HIV/AIDS